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Department of Urology, University of Illinois College of Medicine, Chicago, Illinois 60612
Address all correspondence and requests for reprints to: Gail S. Prins, Ph.D., Department of Urology, M/C 958, University of Illinois, 820 South Wood Street, Chicago, Illinois 60612.
Neonatal exposure to estrogens results in permanent imprints of the rat prostate gland. To delineate the direct target of estrogen action within that tissue, the present study examined estrogen receptor (ER) expression by immunocytochemistry and in situ hybridization. ER were confined to mesenchymal cells in the urogenital sinus and proximal regions of the budding prostate lobes of newborn control rat prostates, and this expression declined after morphogenesis. Exposure to estradiol benzoate on days 1, 3, and 5 resulted in induction of ER expression in periductal smooth muscle cells from the proximal regions out to the distal tips of the developing prostate lobes. This ER expression was associated with the appearance of ER messenger RNA in those cells; thus, it was concluded that the up-regulation of ER by estrogens is mediated at the message level.
Autoregulation of ER expression was next examined in adult prostates that had been exposed to oil or estrogens neonatally. Day 70 rats were castrated and given testosterone with or without estradiol for 7 days before death. Estrogen exposure in adulthood induced low levels of epithelial cell ER in the lateral lobe. Neonatal estrogenization increased the sensitivity of lateral lobe epithelial cells to this autoregulation, as the incidence and intensity of ER immunostaining were markedly increased. No autoinduction of ER was observed in adult ventral or dorsal prostatic lobes.
From the present study we conclude that smooth muscle cells are the targets of estrogen action in the developmentally estrogenized prostate and that estrogen amplifies its own effects through auto-up-regulation of ER. In addition, lateral lobe epithelial cells are sensitive to estrogen up-regulation of ER, which may in part account for the lobe-specific effects observed after neonatal estrogenization of the prostate gland.
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R. A. Jarred, B. Cancilla, G. S. Prins, K. A. Thayer, G. R. Cunha, and G. P. Risbridger Evidence That Estrogens Directly Alter Androgen-Regulated Prostate Development Endocrinology, September 1, 2000; 141(9): 3471 - 3477. [Abstract] [Full Text] [PDF]
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M. K. Dienhart, R. J. Sommer, R. E. Peterson, A. N. Hirshfield, and E. K. Silbergeld Gestational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Induces Developmental Defects in the Rat Vagina Toxicol. Sci., July 1, 2000; 56(1): 141 - 149. [Abstract] [Full Text] [PDF]
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W. Y. Chang, L. Birch, C. Woodham, L. I. Gold, and G. S. Prins Neonatal Estrogen Exposure Alters the Transforming Growth Factor-{beta} Signaling System in the Developing Rat Prostate and Blocks the Transient p21cip1/waf1 Expression Associated with Epithelial Differentiation Endocrinology, June 1, 1999; 140(6): 2801 - 2813. [Abstract] [Full Text]
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W. Y. Chang, M. J. Wilson, L. Birch, and G. S. Prins Neonatal Estrogen Stimulates Proliferation of Periductal Fibroblasts and Alters the Extracellular Matrix Composition in the Rat Prostate Endocrinology, January 1, 1999; 140(1): 405 - 415. [Abstract] [Full Text]
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G. S. Prins, M. Marmer, C. Woodham, W. Chang, G. Kuiper, J.-A. Gustafsson, and L. Birch Estrogen Receptor-{beta} Messenger Ribonucleic Acid Ontogeny in the Prostate of Normal and Neonatally Estrogenized Rats Endocrinology, March 1, 1998; 139(3): 874 - 883. [Abstract] [Full Text] [PDF]
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